2-178834117-G-T

Variant names:

• chr2-178834117-G-T
• rs78585114
• NM_173648.4:c.*56C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173648.4(CCDC141):​c.*56C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000148 in 1,352,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: CCDC141 NM_173648.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.506
• Publications: 0 publications found

Genes affected

CCDC141 (HGNC:26821): (coiled-coil domain containing 141) Predicted to be involved in axon guidance and cell adhesion. Predicted to act upstream of or within centrosome localization and cerebral cortex radially oriented cell migration. Predicted to be located in centrosome; cytoplasm; and plasma membrane. Predicted to be active in neuron projection. [provided by Alliance of Genome Resources, Apr 2022]

CCDC141 Gene-Disease associations (from GenCC):

• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hypogonadotropic hypogonadism

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000287149 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173648.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC141	NM_173648.4	MANE Select	c.*56C>A		3_prime_UTR	Exon 24 of 24	NP_775919.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC141	ENST00000443758.7	TSL:5 MANE Select	c.*56C>A		3_prime_UTR	Exon 24 of 24	ENSP00000390190.2	Q6ZP82-2
	CCDC141	ENST00000922698.1		c.*56C>A		3_prime_UTR	Exon 25 of 25	ENSP00000592757.1
	CCDC141	ENST00000894515.1		c.*56C>A		3_prime_UTR	Exon 23 of 23	ENSP00000564574.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000148 AC: 2 AN: 1352292 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 664938

African (AFR) AF: 0.00 AC: 0 AN: 30782

American (AMR) AF: 0.00 AC: 0 AN: 35202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24596

East Asian (EAS) AF: 0.00 AC: 0 AN: 35300

South Asian (SAS) AF: 0.00 AC: 0 AN: 77312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4708

European-Non Finnish (NFE) AF: 0.00000190 AC: 2 AN: 1054406

Other (OTH) AF: 0.00 AC: 0 AN: 56474

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.96
DANN	Benign	0.39
PhyloP100		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs78585114; hg19: chr2-179698844;